Lin28a uses distinct mechanisms of binding to RNA and affects positively and negatively miRNA levels

Fruzsina Hobor, Jakub Stanislaw Nowak, Angela Velasco, Nila Choudhurry, Gregory Heikel, Alastair Kerr, Andres Ramos, Gracjan Michlewski

Research output: Contribution to journalArticlepeer-review

Abstract


Lin28a inhibits the biogenesis of let-7 miRNAs by triggering the polyuridylation and degradation of their precursors by terminal uridylyltransferases TUT4/7 and 3’-5’ exoribonuclease Dis3l2, respectively. Previously, we showed that Lin28a also controls the production of neuro-specific miRNA-9 via a polyuridylation-independent mechanism. Here we reveal that the sequences and structural characteristics of pre-let-7 and pre-miRNA-9 are eliciting two distinct modes of binding to Lin28a. We present evidence that Dis3l2 controls miRNA-9 production. Finally, we show that the constitutive expression of untagged Lin28a during neuronal differentiation in vitro positively and negatively affects numerous other miRNAs. Our findings shed light on the role of Lin28a in differentiating cells and on the ways in which one RNA-binding protein can perform multiple roles in the regulation of RNA processing.
Original languageEnglish
JournalRNA
Early online date23 Nov 2016
DOIs
Publication statusPublished - 1 Mar 2017

Keywords

  • miRNA-9
  • let-7
  • Lin28a
  • neuronal differentiation

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